Israeli researchers find key to killing leukemia cancer cells

‘Blocking the receptor or other stages in the pathway they activate might be a winning tactic, in the future, in the war against cancers involving B cells.’An Israeli team of scientists have discovered what makes cancer cells which cause chronic lymphocytic leukemia thrive. And using that information, they’ve learned how to kill those cancer cells.

Each year, nearly 27,000 adults and more than 2,000 children in the United States learn that they have leukemia, a malignancy of the blood-forming cells in the bone marrow.

The lifespan of a normal B cell is limited by an internal self-destruct program but, in cancer cells, this mechanism breaks down. B cells that don’t self-destruct can live on to multiply and eventually accumulate in dangerous amounts.

The team from the Weizmann Institute of Science, headed by Prof. Idit Shachar of Weizmann’s Immunology Department and Dr. Michal Haran of the Hematology Institute of the Kaplan Medical Center recently discovered what makes these cancer cells stay alive.

They then launched a targeted attack on the survival mechanism they discovered and succeeded to significantly raise cancer cell mortality rates. Their findings, which appeared recently in Proceedings of the National Academy of Sciences (PNAS), may lead to future treatments for this disease, as well as for other diseases in which B lymphocytes accumulate in the blood.

In previous research, Shachar had found that a specific receptor – a protein on the outer surface of healthy B cells – fulfills a crucial role in helping these cells to survive. She wondered if the same protein might also be a central player in the abnormally high survival rates of cancerous B cells.

Members of Shachar’s research team, including scientists from Yale University and the Garden State Cancer Center in New Jersey, examined B cells taken from chronic lymphocytic leukemia patients. They discovered that, even in the earliest stages of the disease, these cells have an unusually high level of both the survival receptor and another protein that binds to the receptor.

The scientists found that this protein, in binding to the receptor, initiates a series of events within the cell that leads to enhanced cell survival capabilities. For instance, in one of these events, a substance is produced that helps to regulate the cells’ lifespan. This substance causes another protein to be produced, which then prevents the self-destruct program from being activated.

The team treated the chronic lymphocytic leukemia cells with an antibody that attached to the survival receptor, blocking its activity and causing the cancer cell death rate to soar.

The antibodies they used are produced by the firm Immunomedics, in New Jersey, and are currently entering clinical trials for the treatment of several different types of cancer. Following this research, which has revealed the mechanism for the antibody’s actions, the company is planning trials for chronic lymphocytic leukemia, as well.

‘The abnormally elevated levels of this receptor seem to be important factors in the development of this disease, right from the beginning, and they are responsible for the longevity of these cancerous B cells. Blocking the receptor or other stages in the pathway they activate might be a winning tactic, in the future, in the war against cancers involving B cells,” said Shachar.